tbuckley/cabot-search huggingface dataset:
Polyp detection on video colonoscopy using a hybrid 2D/3D CNN
Authors: Juana González-Bueno Puyal, Patrick Brandao, Omer F. Ahmad, Kanwal K. Bhatia, Daniel Toth, Rawen Kader, Laurence Lovat, Peter Mountney, Danail Stoyanov
Journal: Medical Image Analysis (2022)

Colonoscopy is the gold standard for early diagnosis and pre-emptive treatment of colorectal cancer by detecting and removing colonic polyps. Deep learning approaches to polyp detection have shown potential for enhancing polyp detection rates. However, the majority of these systems are developed and evaluated on static images from colonoscopies, whilst in clinical practice the treatment is performed on a real-time video feed. Non-curated video data remains a challenge, as it contains low-quality frames when compared to still, selected images often obtained from diagnostic records. Nevertheless, it also embeds temporal information that can be exploited to increase predictions stability. A hybrid 2D/3D convolutional neural network architecture for polyp segmentation is presented in this paper. The network is used to improve polyp detection by encompassing spatial and temporal correlation of the predictions while preserving real-time detections. Extensive experiments show that the hybrid method outperforms a 2D baseline. The proposed architecture is validated on videos from 46 patients and on the publicly available SUN polyp database. A higher performance and increased generalisability indicate that real-world clinical implementations of automated polyp detection can benefit from the hybrid algorithm and the inclusion of temporal information.
Mitochondrial Stress Induces an HRI-eIF2α Pathway Protective for Cardiomyopathy
Authors: Siting Zhu, Anh Nguyen, Jing Pang, Jun Zhao, Ze’e Chen, Zhengyu Liang, Yusu Gu, Helen Huynh, Yutong Bao, Sharon Lee, Yuval Kluger, Kunfu Ouyang, Sylvia M. Evans, Xi Fang
Journal: Circulation (2022)
Regnase-1 Prevents Pulmonary Arterial Hypertension Through mRNA Degradation of Interleukin-6 and Platelet-Derived Growth Factor in Alveolar Macrophages
Authors: Ai Yaku, Tadakatsu Inagaki, Ryotaro Asano, Makoto Okazawa, Hiroyoshi Mori, Ayuko Sato, Fabian Hia, Takeshi Masaki, Yusuke Manabe, Tomohiko Ishibashi, Alexis Vandenbon, Yoshinari Nakatsuka, Kotaro Akaki, Masanori Yoshinaga, Takuya Uehata, Takashi Mino, Satoshi Morita, Hatsue Ishibashi-Ueda, Akio Morinobu, Tohru Tsujimura, Takeshi Ogo, Yoshikazu Nakaoka, Osamu Takeuchi
Journal: Circulation (2022)

Background: Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension (PH) characterized by obliterative pulmonary vascular remodeling, resulting in right-sided heart failure. Although the pathogenesis of PAH is not fully understood, inflammatory responses and cytokines have been shown to be associated with PAH, in particular, with connective tissue disease-PAH. In this sense, Regnase-1, an RNase that regulates mRNAs encoding genes related to immune reactions, was investigated in relation to the pathogenesis of PH. Methods: We first examined the expression levels of ZC3H12A (encoding Regnase-1) in peripheral blood mononuclear cells from patients with PH classified under various types of PH, searching for an association between the ZC3H12A expression and clinical features. We then generated mice lacking Regnase-1 in myeloid cells, including alveolar macrophages, and examined right ventricular systolic pressures and histological changes in the lung. We further performed a comprehensive analysis of the transcriptome of alveolar macrophages and pulmonary arteries to identify genes regulated by Regnase-1 in alveolar macrophages. Results: ZC3H12A expression in peripheral blood mononuclear cells was inversely correlated with the prognosis and severity of disease in patients with PH, in particular, in connective tissue disease-PAH. The critical role of Regnase-1 in controlling PAH was also reinforced by the analysis of mice lacking Regnase-1 in alveolar macrophages. These mice spontaneously developed severe PAH, characterized by the elevated right ventricular systolic pressures and irreversible pulmonary vascular remodeling, which recapitulated the pathology of patients with PAH. Transcriptomic analysis of alveolar macrophages and pulmonary arteries of these PAH mice revealed that Il6, Il1b , and Pdgfa/b are potential targets of Regnase-1 in alveolar macrophages in the regulation of PAH. The inhibition of IL-6 (interleukin-6) by an anti–IL-6 receptor antibody or platelet-derived growth factor by imatinib but not IL-1β (interleukin-1β) by anakinra, ameliorated the pathogenesis of PAH. Conclusions: Regnase-1 maintains lung innate immune homeostasis through the control of IL-6 and platelet-derived growth factor in alveolar macrophages, thereby suppressing the development of PAH in mice. Furthermore, the decreased expression of Regnase-1 in various types of PH implies its involvement in PH pathogenesis and may serve as a disease biomarker, and a therapeutic target for PH as well.
Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF
Authors: Kieran F. Docherty, Paul Welsh, Subodh Verma, Rudolf A. De Boer, Eileen O’Meara, Olof Bengtsson, Lars Køber, Mikhail N. Kosiborod, Ann Hammarstedt, Anna Maria Langkilde, Daniel Lindholm, Dustin J. Little, Mikaela Sjöstrand, Felipe A. Martinez, Piotr Ponikowski, Marc S. Sabatine, David A. Morrow, Morten Schou, Scott D. Solomon, Naveed Sattar, Pardeep S. Jhund, John J.V. McMurray
Journal: Circulation (2022)

Background: Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism. We also analyzed the effect of dapagliflozin on outcomes, according to iron status at baseline. Methods: Iron deficiency was defined as a ferritin level &lt;100 ng/mL or a transferrin saturation &lt;20% and a ferritin level 100 to 299 ng/mL. Additional biomarkers of iron metabolism, including soluble transferrin receptor, erythropoietin, and hepcidin were measured at baseline and 12 months after randomization. The primary outcome was a composite of worsening heart failure (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Results: Of the 4744 patients randomized in DAPA-HF, 3009 had ferritin and transferrin saturation measurements available at baseline, and 1314 of these participants (43.7%) were iron deficient. The rate of the primary outcome was higher in patients with iron deficiency (16.6 per 100 person-years) compared with those without (10.4 per 100 person-years; P &lt;0.0001). The effect of dapagliflozin on the primary outcome was consistent in iron-deficient compared with iron-replete patients (hazard ratio, 0.74 [95% CI, 0.58–0.92] versus 0.81 [95% CI, 0.63–1.03]; P -interaction=0.59). Similar findings were observed for cardiovascular death, heart failure hospitalization, and all-cause mortality. Transferrin saturation, ferritin, and hepcidin were reduced and total iron-binding capacity and soluble transferrin receptor increased with dapagliflozin compared with placebo. Conclusions: Iron deficiency was common in DAPA-HF and associated with worse outcomes. Dapagliflozin appeared to increase iron use but improved outcomes, irrespective of iron status at baseline. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03036124.
The Portfolio Diet and Incident Type 2 Diabetes: Findings From the Women’s Health Initiative Prospective Cohort Study
Authors: Andrea J. Glenn, Jie Li, Kenneth Lo, David J.A. Jenkins, Beatrice A. Boucher, Anthony J. Hanley, Cyril W.C. Kendall, Aladdin H. Shadyab, Lesley F. Tinker, Steven D. Chessler, Barbara V. Howard, Simin Liu, John L. Sievenpiper
Journal: Diabetes Care (2022)

OBJECTIVE A plant-based dietary pattern, the Portfolio Diet, has been shown to lower LDL cholesterol and other cardiovascular disease risk factors. However, no study has evaluated the association of this diet with incident type 2 diabetes. RESEARCH DESIGN AND METHODS This analysis included 145,299 postmenopausal women free of diabetes at baseline in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study from 1993 to 2021. Adherence to the diet was assessed with a score based on six components (high in plant protein [soy and pulses], nuts, viscous fiber, plant sterols, and monounsaturated fat and low in saturated fat and cholesterol) determined from a validated food-frequency questionnaire. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association of the Portfolio Diet, alongside the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets, with incident type 2 diabetes, with adjustment for potential confounders. RESULTS Over a mean follow-up of 16.0 years, 13,943 cases of incident type 2 diabetes were identified. In comparisons of the highest with the lowest quintiles of adherence, the HRs for risk of incident type 2 diabetes were 0.77 (95% CI 0.72, 0.82) for the Portfolio Diet, 0.69 (0.64, 0.73) for the DASH diet, and 0.78 (0.74, 0.83) for the Mediterranean diet. These findings were attenuated by 10% after additional adjustment for BMI. CONCLUSIONS Greater adherence to the plant-predominant Portfolio, DASH, and Mediterranean diets was prospectively associated with lower risk of type 2 diabetes in postmenopausal women.
Nationally Subsidized Continuous Glucose Monitoring: A Cost-effectiveness Analysis
Authors: Anthony J. Pease, Sophia Zoungas, Emily Callander, Timothy W. Jones, Stephanie R. Johnson, D. Jane Holmes-Walker, David E. Bloom, Elizabeth A. Davis, Ella Zomer
Journal: Diabetes Care (2022)

OBJECTIVE The Continuous Glucose Monitoring (CGM) Initiative recently introduced universal subsidized CGM funding for people with type 1 diabetes under 21 years of age in Australia. We thus aimed to evaluate the cost-effectiveness of this CGM Initiative based on national implementation data and project the economic impact of extending the subsidy to all age-groups. RESEARCH DESIGN AND METHODS We used a patient-level Markov model to simulate disease progression for young people with type 1 diabetes and compared government-subsidized access to CGM with the previous user-funded system. Three years of real-world clinical input data were sourced from analysis of the Australasian Diabetes Data Network and National Diabetes Services Scheme registries. Costs were considered from the Australian health care system’s perspective. An annual discount rate of 5% was applied to future costs and outcomes. Uncertainty was evaluated with probabilistic and deterministic sensitivity analyses. RESULTS Government-subsidized CGM funding for young people with type 1 diabetes compared with a completely user-funded model resulted in an incremental cost-effectiveness ratio (ICER) of AUD 39,518 per quality-adjusted life-year (QALY) gained. Most simulations (85%) were below the commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained in Australia. Sensitivity analyses indicated that base-case results were robust, though strongly impacted by the cost of CGM devices. Extending the CGM Initiative throughout adulthood resulted in an ICER of AUD 34,890 per QALY gained. CONCLUSIONS Providing subsidized access to CGM for people with type 1 diabetes was found to be cost-effective compared with a completely user-funded model in Australia.
Ion elemental-optimized layered double hydroxide nanoparticles promote chondrogenic differentiation and intervertebral disc regeneration of mesenchymal stem cells through focal adhesion signaling pathway
Authors: Zhaojie Wang, Huiyi Yang, Xu Xu, Hongxing Hu, Yuxin Bai, Jian Hai, Liming Cheng, Rongrong Zhu
Journal: Bioactive Materials (2022)

Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current clinical treatments do not restore the biological structure and inherent function of the disc. The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD. We synthesized biocompatible layered double hydroxide (LDH) nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining, qPCR, and immunofluorescence analyses. LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model. Repair and regeneration evaluated using X-ray, magnetic resonance imaging, and tissue immunostaining 4-12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure. Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix (ECM) and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration. The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment.
Benefits and Risks Associated With Continuation of Anti–Tumor Necrosis Factor After 24 Weeks of Pregnancy in Women With Inflammatory Bowel Disease
Authors: Antoine Meyer, Anke Neumann, Jérôme Drouin, Alain Weill, Franck Carbonnel, Rosemary Dray-Spira
Journal: Annals of Internal Medicine (2022)

Continuation of biologics for inflammatory disorders during pregnancy is still a difficult decision. Many women with inflammatory bowel diseases (IBDs) stop anti-tumor necrosis factor (anti-TNF) treatment after 24 weeks.To evaluate the benefits and risks of anti-TNF continuation after 24 weeks of pregnancy for mothers with IBD and their offspring.Target trial emulation between 2010 and 2020.Nationwide population-based study using the Système National des Données de Santé.All pregnancies with birth exposed to anti-TNF between conception and 24 weeks of pregnancy in women with IBD.Continuation of anti-TNF after 24 weeks of pregnancy.Occurrence of maternal IBD relapse up to 6 months after pregnancy, adverse pregnancy outcomes, and serious infections in the offspring during the first 5 years of life was compared according to anti-TNF continuation after 24 weeks of pregnancy using inverse probability-weighted marginal models.A total of 5293 pregnancies were included; among them, anti-TNF treatment was discontinued before 24 weeks for 2890 and continued beyond 24 weeks for 2403. Continuation of anti-TNF was associated with decreased frequencies of maternal IBD relapse (35.8% vs. 39.0%; adjusted risk ratio [aRR], 0.93 [95% CI, 0.86 to 0.99]) and prematurity (7.6% vs. 8.9%; aRR, 0.82 [CI, 0.68 to 0.99]). No difference according to anti-TNF continuation was found regarding stillbirths (0.4% vs. 0.2%; aRR, 2.16 [CI, 0.64 to 7.81]), small weight for gestational age births (13.1% vs. 12.9%; aRR, 1.01 [CI, 0.88 to 1.17]), and serious infections in the offspring (54.2 vs. 50.2 per 1000 person-years; adjusted hazard ratio, 1.08 [CI, 0.94 to 1.25]).Algorithms rather than clinical data were used to identify patients with IBD, pregnancies, and serious infections.Continuation of anti-TNF after 24 weeks of pregnancy appears beneficial regarding IBD activity and prematurity, while not affecting neonatal outcomes and serious infections in the offspring.None.
Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)
Authors: Jeffrey S. Weber, Dirk Schadendorf, Michele Del Vecchio, James Larkin, Victoria Atkinson, Michael Schenker, Jacopo Pigozzo, Helen Gogas, Stéphane Dalle, Nicolas Meyer, Paolo A. Ascierto, Shahneen Sandhu, Thomas Eigentler, Ralf Gutzmer, Jessica C. Hassel, Caroline Robert, Matteo S. Carlino, Anna Maria Di Giacomo, Marcus O. Butler, Eva Muñoz-Couselo, Michael P. Brown, Piotr Rutkowski, Andrew Haydon, Jean-Jacques Grob, Jacob Schachter, Paola Queirolo, Luis de la Cruz-Merino, Andre van der Westhuizen, Alexander M. Menzies, Sandra Re, Tuba Bas, Veerle de Pril, Julia Braverman, Daniel J. Tenney, Hao Tang, Georgina V. Long
Journal: Journal of Clinical Oncology (2022)

Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma.In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for ≤ 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level < 1% subgroup.At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression < 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients.Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment.
Adenoma Detection Rate and Risk for Interval Postcolonoscopy Colorectal Cancer in Fecal Immunochemical Test–Based Screening
Authors: Pieter H.A. Wisse, Nicole S. Erler, Sybrand Y. de Boer, Bert den Hartog, Marco Oudkerk Pool, Jochim S. Terhaar sive Droste, Claudia Verveer, Gerrit A. Meijer, Iris Lansdorp-Vogelaar, Ernst J. Kuipers, Evelien Dekker, Manon C.W. Spaander
Journal: Annals of Internal Medicine (2022)

Background: The adenoma detection rate (ADR) is an essential quality indicator for endoscopists performing colonoscopies for colorectal cancer (CRC) screening as it is associated with postcolonoscopy CRCs (PCCRCs). Currently, data on ADRs of endoscopists performing colonoscopies in fecal immunochemical testing (FIT)-based screening, the most common screening method, are scarce. Also, the association between the ADR and PCCRC has not been demonstrated in this setting. Objective: To evaluate the association between the ADR and PCCRC risk in colonoscopies done after a positive FIT result. Design: Population-based cohort. Setting: Dutch, FIT-based, CRC screening program. Participants: Patients undergoing colonoscopy, done by accredited endoscopists, after a positive FIT result. Measurements: Quality indicator performance and PCCRC incidence for colonoscopies in FIT-positive screenees were assessed. The PCCRCs were classified as interval, a cancer detected before recommended surveillance, or noninterval. The association between ADR and interval PCCRC was evaluated with a multivariable Cox regression model and PCCRC incidence was determined for different ADRs. Results: 362 endoscopists performed 116 360 colonoscopies with a median ADR of 67%. In total, 209 interval PCCRCs were identified. The ADR was associated with interval PCCRC, with an adjusted hazard ratio of 0.95 (95% CI, 0.92 to 0.97) per 1% increase in ADR. For every 1000 patients undergoing colonoscopy, the expected number of interval PCCRC diagnoses after 5 years was approximately 2 for endoscopists with ADRs of 70%, compared with more than 2.5, almost 3.5, and more than 4.5 for endoscopists with ADRs of 65%, 60%, and 55%, respectively. Limitation: The relative short duration of follow-up (median, 52 months) could be considered a limitation. Conclusion: The ADR of endoscopists is inversely associated with the risk for interval PCCRC in FIT-positive colonoscopies. Endoscopists performing colonoscopy in FIT-based screening should aim for markedly higher ADRs compared with primary colonoscopy. Primary Funding Source: None.
SGLT2 Inhibition, Choline Metabolites, and Cardiometabolic Diseases: A Mediation Mendelian Randomization Study
Authors: Min Xu, Jie Zheng, Tianzhichao Hou, Hong Lin, Tiange Wang, Shuangyuan Wang, Jieli Lu, Zhiyun Zhao, Mian Li, Yu Xu, Guang Ning, Yufang Bi, Weiqing Wang
Journal: Diabetes Care (2022)

OBJECTIVE To investigate the causal role of choline metabolites mediating sodium–glucose cotransporter 2 (SGLT2) inhibition in coronary artery disease (CAD) and type 2 diabetes (T2D) using Mendelian randomization (MR). RESEARCH DESIGN AND METHODS A two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on CAD and T2D; 2) causal effects of three choline metabolites, total choline, phosphatidylcholine, and glycine, on CAD and T2D; and 3) mediation effects of these metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Summary statistics for metabolites were from UK Biobank, CAD from CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) consortium, and T2D from DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the FinnGen study. RESULTS SGLT2 inhibition (per 1 SD, 6.75 mmol/mol [1.09%] lowering of HbA1c) was associated with lower risk of T2D and CAD (odds ratio [OR] 0.25 [95% CI 0.12, 0.54], and 0.51 [0.28, 0.94], respectively) and positively with total choline (β 0.39 [95% CI 0.06, 0.72]), phosphatidylcholine (0.40 [0.13, 0.67]), and glycine (0.34 [0.05, 0.63]). Total choline (OR 0.78 [95% CI 0.68, 0.89]) and phosphatidylcholine (OR 0.81 [0.72, 0.91]) were associated with T2D but not with CAD, while glycine was associated with CAD (0.94 [0.91, 0.98]) but not with T2D. Mediation analysis showed evidence of indirect effect of SGLT2 inhibition on T2D through total choline (0.91 [0.83, 0.99]) and phosphatidylcholine (0.93 [0.87, 0.99]) with a mediated proportion of 8% and 5% of the total effect, respectively, and on CAD through glycine (0.98 [0.96, 1.00]) with a mediated proportion of 2%. The results were well validated in at least one independent data set. CONCLUSIONS Our study identified the causal roles of SGLT2 inhibition in choline metabolites. SGLT2 inhibition may influence T2D and CAD through different choline metabolites.